To study the pharmacokinetic properties, safety and viral resistance pattern of the combination of tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their newborns, with a view to prevention of mother-to-child transmission (PMTCT) of HIV-1 in Africa and Asia.

Single-dose nevirapine (sdNVP) is the option of choice for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of sdNVP results in resistance mutations with an estimated frequency at of least 15 to 70% in women at W4-W6 postpartum. These mutations could compromise the success of subsequent treatments of mother and child with antiretroviral combinations that include NVP. Pre-clinical and clinical studies suggest that a combination of TDF and FTC, drugs with interesting pharmacokinetic properties that may be a useful alternative or complement to sdNVP.

The objectives are to study the pharmacokinetic properties, safety and viral resistance pattern of the combination of tenofovir disoproxil fumarate {TDF, 600 mg} and emtricitabine {FTC, 400 mg}) in HIV-1-infected pregnant women and their newborns, with a view to prevention of mother-to-child transmission (PMTCT) of HIV-1 in Africa and Asia.

Phase II trial, multicentre, open-label will be conducted in two steps with 30 mother-infant pairs per step and with a balanced allocation in Abidjan (Côte d'Ivoire), Soweto (South Africa) and Phnom Penh (Cambodia):

Step 1: administration of TDF/FTC to the mother; Step 2: administration of TDF/FTC to the mother and the newborn.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Women received voluntary counselling and testing and knows her serological status

HIV-1 or HIV-1+2 infection whose serological diagnosis is confirmed by two samples

Aged 18 years or over on the day of the inclusion

Ongoing pregnancy of between 28 and 38 weeks of gestation from the day of the inclusion. This estimate will be based on the date of the last menstruation, or ultrasound scan, or uterine height measurement

Indication for antiretroviral treatment in the Prevention of Mother-To-Child-Transmission (PMTCT), in line with international or national recommendations in force: WHO's clinical stage 1, 2 and CD4≥200/mm3or stage 3 and CD4≥350/mm3 (No indication of antiretroviral treatment)

Haemoglobin over 8 g/dL in the month preceding inclusion

Blood creatinine less than three times the upper limit of normal values

Creatinine clearance > 49 mL/min

Transaminases (ALAT or ASAT) less than five times the upper limit of normal values

Neutrophils ≥750/mm3

No hypersensitivity to emtricitabine, tenofovir, tenofovir disoproxil fumarate, zidovudine, nevirapine or to the excipients

Signed informed-consent form by the woman and, by the father of the child to be born

Planned delivery in a hospital setting and stay for at least 72 hours afterwards

Agreement to take no other medication during the trial without telling the investigator

Naïve to all antiretroviral treatment and to antiretroviral prophylaxis for PMTCT during a previous pregnancy

Permanent residence close enough to the study centre to enable follow-up as stipulated in the protocol

Exclusion Criteria:

Under 18 years of age

Infected by HIV-2 alone

One of the two parents (father) refuses to sign the consent to participate (available only for Abidjan and Phnom Penh) or the mother ( for the Soweto site)

Severe pregnancy disease (pre-eclampsia) that is life-threatening for the mother, the infant, or for both

Severe vomiting preventing ingestion of tablets

Refuses to give birth at a study site and to stay in hospital for at least 72 hours afterwards

Renal insufficiency defined by blood creatinine more than three times the upper limit of normal values

Creatinine clearance under or equal to 49 mL/min

Hepatic insufficiency defined by transaminases (ALAT or ASAT) more than five times the upper limit of normal values

Neutrophils <750/mm3

Haemoglobin <8 grams/dL in the month preceding inclusion

Hypersensitivity to emtricitabine, tenofovir, tenofovir disoproxil fumarate, zidovudine, nevirapine or to the excipients

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334256